The present invention generally relates to a method and device for flowing a liquid on a surface.
There are many applications in which it is desirable to flow a liquid on a surface. An example of such an application is in patterning or other processing of surfaces. Patterning and processing of surfaces with liquids is becoming increasingly important in a range of fields, including chemistry, biology, biotechnology, materials science, electronics, and optics. Patterning a surface by applying a liquid to the surface typically involves confinement of the liquid to defined regions of the surface.
A surface is typically wettable by a liquid if the contact angle between a drop of the liquid and the surface is less than 90 degrees. A channel for carrying a liquid is typically wettable if the channel exerts a negative pressure on the liquid when partially filled. Such a negative pressure promotes filling of the channel by the liquid. In a channel having a homogeneous surface, a negative pressure arises if the contact angle between the liquid and the surface is less than 90 degrees. A surface is typically regarded as more wettable if the contact angle between the surface and the liquid is smaller and less wettable if the contact angle between the surface and the liquid is higher.
One conventional surface patterning technique is lithography. In lithography, a mask is usually applied to the surface to be patterned. Apertures are formed in the mask to define regions of the surface to be exposed for treatment. Those areas of the surface remaining covered by the mask are protected from treatment. The mask is typically formed from a patterned layer of resist material. The surface carrying the mask is then typically immersed in a bath of chemical agents for treating the exposed regions of the surface. Lithography is a relatively expensive process to perform, involving multiple steps. With the possible exception of in situ synthesis of short DNA strands, lithography is generally unsuitable for handling and patterning biomolecules on surfaces. Lithography is also unsuitable for simultaneously processing surfaces with different chemicals in parallel, as described by Whitesides, Annu. Rev. Biomed. 3 (2001), 335-373.
There can be incompatibility between different process steps or chemicals used in lithography and between various surface layers processed by lithography.
Another conventional surface patterning technique is drop delivery. Drop delivery systems, such as pin spotting systems, ink jet systems, and the like, typically project a relatively small volume of liquid onto a specific location on a surface. See Shena, M., “Microarray biochip technology”, Eaton Publishing 2000. However, these systems have limited resolution due to spreading of dispensed drops on the surface. Additionally, the quality of patterns formed by such systems is strongly limited by drying of the delivered liquid, as described by Smith, J. T., “Spreading Diagrams for the Optimization of Quill Pin Printed Microarray Density”, Langmuir, 18 (2002), p 6289-6293.
These systems are not generally useful for dissolving or extracting materials from a surface. Additionally, these systems do not facilitate a flow of liquid over a surface. Furthermore, these systems are not suited to process a surface sequentially with several liquids.
PCT WO 01/63241 A2 describes a surface patterning technique involving a device having a channel with a discharge aperture. A matching pillar is engaged with the discharge aperture to promote deposition of molecules on the top surface of the pillar. A disadvantage with this device is that it is not possible to vary patterning conditions for different pillars individually. Another disadvantage is that it is not capable of establishing a flow on a surface. Exposure of the surface to the liquid needs to be sufficiently long to allow reagents to reach the surface by diffusion. The method also requires a surface with pillars matching the aperture. Fabrication of such a surface requires expensive clean-room equipment and etching tools. This can increase cost per patterned surface. Precise alignment of the device with the pillars before engagement is required. Additionally, the pillars need pretreatment to ensure the confinement of the liquid. Spacing between the discharge aperture and the pillars needs external control.
Yet another conventional surface patterning technique involves application of a microfluidic device to the surface. An example of such a device is described in U.S. Pat. No. 6,089,853. The device described therein can establish a flow of liquid over a surface. The flow can be created via capillary action in the device. The device can treat a surface with multiple different liquids in parallel. However, the device must be sealed to the surface in the interests of confining the liquid to the region of the surface to be treated. Such confinement allows the formation of patterns with relatively high contrast and resolutions. These are desirable qualities where biomolecules are patterned on a surface for biological screening and diagnostic purposes.
In addition, the device must be placed on the surface to be treated and sealed around the processing regions before it can be filled with treatment liquid. If the flow is created by capillary action, other problems arise. For example, service ports in the device must be filled with treatment liquid for each patterning operation. In addition, only one liquid can be delivered to each channel in the device. The liquid cannot be flushed out of the or each channel before separation of the device from the surface. Furthermore, the treatment liquid tends to spread away from the regions of the surface to be treated during removal of the device from the surface.
Also, the device is not suitable for processing a surface sequentially with several liquids. If the flow is created by external actuation, such as pressurization, electric fields, or the like, then other problems arise. For example, an individual connection from the actuator must be made to each channel in the device. Such connections to peripheral equipment limit the density of channels that can be integrated into the device and individually addressed. Pumping, valving, and control complexity increases as the number of channels increases. External connections create dead volume between the device and external actuators because of the intervening conduits.
Another microfluidic device for localized processing of a surface is described in IBM Technical Disclosure Bulletin reference RD n446 Article 165 Page 1046. This device is similar to that described in U.S. Pat. No. 6,09,853. The device permits several liquids to be flushed in sequence over the same surface area without requiring separation of the device from the surface. Such a device is thus useful for chemical and biological reactions involving the sequential delivery of several liquids. A disadvantage associated with this device however is that it must be sealed around the region of the surface to be treated before filling. Another disadvantage is that the liquids cannot be filled prior to application on the device to the surface. Each additional step requires supplementary filling of the relevant liquid. Another disadvantage is that the device cannot be removed from the surface while the service ports contain liquid without liquid spreading over the surface beyond the region to be exposed.
Another conventional device for confining liquids to a predefined pattern between a top and bottom surface without involving a seal is described in European Patent 0 075 605. This device is useful for performing optical analysis of a liquid trapped between the top and bottom surface. However, the device requires predefined topographical or chemical patterns on both the top and bottom surfaces. Also, the device, having no inlet or outlet ports, is not suitable for the transport of liquids.
Another device for guiding liquids along a predetermined path is described in WO 99/56878. This device can flow several liquids simultaneously over a surface without involving seal to confine the liquids. However, a disadvantage of this device is that separation gaps between paths have to be capillary inactive. This limits path sizes to greater than 1 mm. Otherwise meniscus pressures produce uncontrolled spreading of liquid. Another disadvantage of this device is that liquid is not retained after separation and can instead spread over the surface. A further disadvantage of this device is that liquid delivery requires an external connection to each path. Cumbersome peripheral flow control devices are also required.
Yet another method for guiding liquid along a surface without involving a seal is described in Zhao et al., Science, Vol. 291 (2001), p. 1023-1026. Here, the surface is patterned with a wettability pattern. Specifically, two wettable paths mirroring each other are defined on otherwise non-wettable top and bottom surfaces. This produces “virtual” channels without lateral walls that can have micrometer width. A disadvantage of this method is that it requires wettability patterns on both the top and bottom surfaces. Additionally, the wettability contrast between the two patterns needs to be very high, and requires both non-wettable areas on the top and bottom surfaces and highly wettable areas within the virtual channel. Furthermore, the two patterns have to match each other exactly in shape and alignment. Capillary action can used to fill the channels, but the liquid cannot be removed or exchanged. This method is also susceptible to uncontrolled spreading of liquid because it is relatively difficult to produce sufficiently non-wettable surfaces. A external pump may be used to deliver the liquid, but if the pump pressure exceeds a relatively low level, liquid will overflow the defined flow path. Furthermore, external pumping requires external connections to each flow path, thus limiting integration. As indicated earlier, external connections create dead volume in pump connecting conduits.
It would be desirable to provide a technique for flowing a liquid over a surface in a more versatile and convenient manner.